James Andreassi’s long locks swing forward, his expression hardens, and his gestures become more dramatic: The actor is slipping into his part seemingly without realizing it. In a dressing room at Lyric Stage Company, he’s talking about his role as Ludwig van Beethoven and about the composer’s “Diabelli Variations.”

“The great biographical research to be done is to listen to the music. I just get lost in it,” he says. “So much of the work was produced when he was deaf, and that frustration, that anger, is apparent.”

The 54-year-old actor plays the composer in Moisés Kaufman’s “33 Variations,” which begins performances Friday at Lyric Stage Company. Andreassi, who grew up in Roslindale and Milton, is the founder and artistic director of Elm Shakespeare Company
in New Haven, but this is his fourth role in Boston in the last couple of years.

“Variation 32, because of the text, is the piece of music that I’m most immersed in. As an actor you’re always looking for the emotional truth, and for me there is, just in the way he attacks the piano in that piece, there is an anger,” he says.

“But the last 20 seconds of the piece are about release. Or at least that’s the way it’s evolving in my head.”

Paula Plum plays the central character in “33 Variations,” a musicologist who becomes obsessed with Beethoven’s work as she faces her diagnosis of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. Why, the scholar wonders, did Beethoven become so involved in writing variations on a single waltz theme even as he sank into deafness? And she becomes determined to figure him out, despite the dramatic progression of her own illness.

“I never had to research so much for a part, ever,” Plum says by phone. “Because not only have I had to know as much as I can about Beethoven . . . but I’ve had to follow the progress of ALS as best I can.”

In addition to a lot of reading, she’s been helped by Steve Saling, a local architect who was diagnosed with ALS in 2006 and helped create an ALS-friendly group residence in Chelsea while his own disease progressed.

ALS, however, is not the play’s sole subject. Plum says the piece has “an enormous heart to it. It digs into what it means to be creative and obsessed.”

In performance, Andreassi has to incarnate that artistic spirit.

“The journeys these characters make are not easy,” he says. “The physical transformation for her is stunning. As an actor, you make a leap of faith every time. And I’m playing Beethoven, for [expletive] sake! How does one communicate genius and misery and all the things that need to be communicated?”

“33 Variations” reunites Andreassi and Plum, who played the title roles in “Antony and Cleopatra” for Actors’ Shakespeare Project
in the spring of 2011. That production, both say, was a peak professional experience.

Globe critic Don Aucoin wrote in his review: “There is an erotic charge to their scenes together; Andreassi and Plum persuade us that the love between Antony and Cleopatra is not tactical but genuine, a kind of mutual trance that neither can escape, even though it eventually spells doom for both.”

Kaufman’s play is a more solitary undertaking, Andreassi notes.

“We don’t have much to do together onstage until the very end of the play,” he says. “She’s on when I’m off. [But] both of us like to stay in the rehearsal room a lot. So the way we’re working with each other now is that I’ll come off and say to her, ‘Are you buying any of this?’ . . . We both know we’re in the deep end of the pool, and we both know we have each other’s back, and that makes it safe to jump in the water.”

One thing the former Tufts football player won’t have to do in “33 Variations” is play the piano, a skill Kaufman’s script does not require. “I suppose his thought was [that] finding an actor that’s the right type who’s also a virtuoso pianist would be tough,” Andreassi speculates. Instead, there’s an onstage pianist, Catherine Stornetta, to provide the music.

The pianist, too, faces some challenges, Andreassi learned from his research: “Beethoven was such an egoist that he wrote pieces giggling in the hope they would be difficult to play,” he says.

Plum, on the other hand, was seeking harmony when she first sat down with Andreassi, before “Antony and Cleopatra” rehearsals began. She had wanted to play Cleopatra for many years before that production, but she also wanted to be sure she and Andreassi would be a good match onstage. So they met at an Au Bon Pain. “It was instantly obvious that he would be a wonderful Antony,” she recalls.

“Jim and I have such a compatibility onstage. I just sort of intuitively know we were meant to work together,” says Plum, who cast him as Macduff when she directed “Macbeth” last fall for Actors’ Shakespeare Project.

“He’s kind of a force of nature,” she says. “He’s one of those really masculine men who plays those heroic roles really well.”

The two performers say they are alike in a strange way. As Plum puts it, “What’s weird about actors is that the most extroverted actors are really profound introverts . . . we’re hyper-vulnerable and sensitive on the inside.”

Andreassi notes that he and Plum have each been married for 32 years. His wife is Margaret Andreassi, managing director of Elm Shakespeare, and Plum’s husband is actor Richard Snee. “We both recognize that safety as fundamental to our work,” says Andreassi, who also played Sir Toby in Actors’ Shakespeare Project’s “Twelfth Night” last season.

Lyric Stage artistic director Spiro Veloudos remembers reading a review of “Antony and Cleopatra.” Otherwise, he says, he knew nothing about Andreassi until the actor appeared at a series of showcase auditions organized by StageSource last spring.

“His hair was about as long as it is now, and I went, ‘Wow, you look like Beethoven,’” Veloudos says. “And then it was, wow, I just hope he can act. And he gave a great audition.”